P-071: Hevylite in the multiple myeloma patient pathway

Introduction: The majority of multiple myeloma (MM) patients are now achieving very deep responses. The most sensitive disease detection techniques are currently bone marrow assays. However, as bone marrow (BM) sampling is invasive and unpleasant for patients it is important to investigate whether blood-based assays could be equally or more informative of disease status. The HevyliteTM assay (The Binding Site, UK) evaluates serum heavy/light chains (HLC) for IgG, IgA and IgM M-proteins. This study assessed whether the HLC assay could act as an effective marker for disease in the bone marrow of treated MM patients and evaluate the prognostic utility of HLC measurements at best response and relapse time points.

Methods: Patients: 104 MM (IgG or IgA), either prior to transplant or during chemotherapy. Median follow up = 18 months. Routine M-proteins were performed alongside HLC testing. A BM flow cytometry MRD assay was tested in parallel if relevant. Disease response was set according to IMWG criteria. Baseline was the initial sample taken post-therapy.

Results: At pre- and post-transplant there was significant agreement between HLC measurements and BM-MRD, with uHLC being the most sensitive (86%) and HLCr the most specific (100%). Survival analysis showed significantly inferior survival in patients with abnormal uHLC or HLCr results post-transplant.
Follow up HLC values correlated with depth of response, uHLC was abnormal in 60% of complete response (CR) patients. At best response uHLC gave a significant difference in survival, with this significance remaining in CR patients only. Addition of the free light chain assay into analysis did not improve the significance of survival differences.
For relapsed patients, comparisons of M-protein with HLC parameters at best response vs. prior to clinical relapse showed uHLC was the only marker to be significantly different between the two time points in IgG and IgA patients. Patients in stable disease did not experience a significant change in uHLC levels.
In all analyses the HLC assay showed increased sensitivity and utility over the M-protein technique.

Conclusions: Blood-based assays can be used prior to bone marrow analysis to help influence decisions and improve patient experience. This strategy can also impact patient follow up post initial treatment:
1. At best response, an abnormal uHLC or HLCr suggests a positive MRD status, meaning a possible reduction or delay in the requirement for bone marrow assessment.
2. All patients in ≥VGPR should have HLC performed alongside conventional assays during follow up.
3. If uHLC values become abnormal over follow up then it should be assumed that the patient is about to undergo relapse.
The measurement of HLC values increases the sensitivity for detecting MRD, giving further clarification of response status and predicting early relapse.